Pressure apron direct injection catheter

ABSTRACT

A pressure apron for insitu plug formation is provided. In one embodiment an injection tube having a first channel and a piercing tip is provided, the first channel in fluid communication with a pressure source. In this embodiment, the injection catheter may also include a pressure apron with a tissue-mating surface. In another embodiment a medical kit for delivering a therapeutic is provided. This medical kit may include a catheter having a channel and a piercing tip, the piercing tip in fluid communication with a pressure source and slidably placed in the channel. The catheter in this embodiment may include a pressure apron with a tissue-mating source while a therapeutic may be included with the kit.

FIELD OF THE INVENTION

[0001] The present invention relates to the direct delivery oftherapeutic to a target tissue. More specifically, the present inventionrelates to an injection device and method that employ a pressure apronthat can sealably engage a target tissue during the introduction oftherapeutic to the target tissue.

BACKGROUND OF THE INVENTION

[0002] Therapeutics are often delivered directly to target areas ofdiseased tissue in various contemporary medical procedures. This directdelivery has proven to be an advantageous approach when treatingnumerous medical conditions. One advantage of this procedure is thatonly the target tissue may be exposed to the therapeutic while anotheris that a controlled dose of therapeutic may be directly delivered tothe target tissue.

[0003] Due to innumerable variables including viscosity of thetherapeutic, receptivity of the target tissue, and the activecontraction and expansion of the target tissue, therapeutic delivered toa target site may not remain in place both during and after itsdelivery. It may, instead, diffuse away, being leaked or ejected fromthe area surrounding the delivery point. Specifically, for example, whentherapeutic is injected into an actively contracting tissue such as themyocardium of the heart, the therapeutic may be ejected or squeezed outthrough its point of entry by the repeated expansion and contraction ofthe heart muscle. This unintended and unwanted leakage can result in anunascertainable dosage of therapeutic being delivered and arbitraryinteraction between leaked therapeutic and neighboring tissue andmuscle.

SUMMARY OF THE INVENTION

[0004] An injection catheter for direct injection into a body tissue isprovided in one embodiment of the present invention. In this embodimentthe injection catheter may include an injection tube having a firstchannel and a piercing tip, the first channel in fluid communicationwith a pressure source. Furthermore, the injection catheter may alsoinclude a pressure apron with a tissue-mating surface, wherein theinjection tube can extend beyond the tissue-mating surface in at leastcertain positions.

[0005] In another embodiment a medical kit for delivering a therapeuticis provided. This medical kit may include a catheter having a channeland a piercing tip, the piercing tip in fluid communication with apressure source, the piercing tip slidably placed in the channel. Thecatheter in this embodiment may include a pressure apron with atissue-mating source. A therapeutic may be included with the kit aswell.

[0006] A system for preventing leakage of material from a body tissueduring the injection of a therapeutic may be provided in yet anotherembodiment. A system in accord with this embodiment may include acatheter with a channel, a pressure apron surrounding the channel, and apiercing tip retractably positioned within the channel, the pressureapron having a tissue-mating surface.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007]FIG. 1 is an enlarged partial cross-sectional view of a singlechannel injection catheter having an injection tube with a piercing tipin accord with an embodiment of the present invention.

[0008]FIG. 2 is a sectional view along line 2-2 of FIG. 1.

[0009]FIG. 3 is a partial cross-sectional view of the injection catheterof FIG. 1, with the injection tube extending from the pressure apron.

[0010]FIGS. 4A through 4D each show partial cross-sectional viewsillustrating individual steps of a method of using a dual-channelinjection catheter in accord with another embodiment of the presentinvention.

[0011]FIG. 5 is a side partial cross-sectional view of a dual-channelinjection catheter in accord with yet another embodiment of the presentinvention.

[0012]FIG. 6 is a cross-sectional view along line 6-6 of FIG. 5.

[0013]FIG. 7 is a partial cross-sectional view of a human heartincluding an injection catheter in accord with another embodiment of thepresent invention.

[0014]FIG. 8 is a side view of a dual-channel injection catheter inaccord with another embodiment of the present invention.

[0015]FIG. 9 is a graph of a scaling group showing theoretical deliveredmass versus observed delivered mass.

[0016]FIG. 10 is a graph of a control group showing a control systemversus observed delivered mass.

DETAILED DESCRIPTION

[0017]FIG. 1 is an enlarged partial cross-sectional side view of asingle channel or lumen injection catheter 100 having a pressure apron130 in accord with an embodiment of the present invention. In theembodiment of FIG. 1 a single channel injection tube 110 is enclosed bycatheter wall 150 of the catheter 100 and shares a concentriclongitudinal axis with the catheter 100. The single channel injectiontube 110 in this embodiment has a tapered end terminating in a piercingtip 120. Also labeled in this figure are the internal lumen 140 of thecatheter 100 and the tissue-mating surface 160 of the pressure apron130.

[0018] The injection catheter 100 in this embodiment may be used todeliver therapeutic and in-situ plug forming material to a target site.Accordingly, in one embodiment, the single channel injection tube 110may be coupled to a pressure source, such as a pump or a syringe thatcan be used to force therapeutic and in-situ plug forming material downthe internal channel of the injection tube 110 to a target site. Thistherapeutic and plug forming material may be fed into the channel duringthe medical procedure or before hand. If it is delivered during theprocedure it may be directly injected into the pump being used as apressure source. Alternatively, if it is preloaded, it may be loadedjust prior to the initiation of the procedure or sometime earlier thanthat. As described in greater detail below the therapeutic beingdelivered may be one of numerous available therapeutics and the in-situplug forming material may include an alginate and calcium as well beingone of numerous other plug forming compounds.

[0019] The injection catheter 100 in this embodiment may be used todeliver therapeutic to a target site located deep within the body.Consequently, it may be preferable to form the catheter 100 and theinjection tube 110 from suitably rigid materials that will allowsufficient control but remain flexible so that they may be maneuveredwithin the body by the medical practitioner performing the procedure.Such suitable materials may include fabricating the catheter wall 150and injection tube 110 from a rigid polymer while making the piercingtip 120 from a more rigid material such as nitinol so that it mayreadily pierce into target tissue.

[0020] Surrounding the catheter 100 in this embodiment is a pressureapron 130. This pressure apron 130 has a tissue-mating surface 160 thatmay sealably engage a target tissue during use. In order to promote atight seal with a target tissue this tissue-mating surface may have anadhesive placed on it and it may be configured or adapted to promote itssealing engagement with a target tissue. For instance, this adaptationmay include adding a profiled surface to the pressure apron and formingit in the shape of a suction cup, both of which can enhance its abilityto engage the target tissue. In either case, it is preferable that thepressure apron does not have pointed edges that can snare or damage alumen wall when the catheter is being snaked to the target site.

[0021] Rather than being two discrete structures, the pressure apron 130and the catheter wall 150 may also be formed from the same material. Ineither case, it is preferable that the materials chosen be sufficientlyrigid to provide for catheter control while at the same time beingsufficiently flexible to allow for maneuverability during the procedureand sealability with the target tissue.

[0022]FIG. 2 is a cross-sectional view taken along line 2-2 of FIG. 1.In FIG. 2 the catheter wall 150, pressure apron 130, and injection tube110 can be seen. While the cross-section in this view makes it clearthat the lumen and the channel are circular these structures could haveother cross-sectional configurations including oval, stellate,rectangular, and side-by-side obround orientations.

[0023]FIG. 3 is a side partial cross-sectional view of the catheter fromFIG. 1. In FIG. 3 the injection tube 110 is shown protruding from thetissue-mating surface 160 of the pressure apron 130 as may occur duringthe deployment of therapeutic to a target tissue in the body. As can beseen in FIG. 3, the most distal point of the injection tube 110 formsthe piercing tip 120.

[0024] The pressure apron 130 in this embodiment can be formed ofbiocompatible polymeric or metallic materials. Examples of the materialsthat can be used to form the pressure apron 130 include silicones,nylons, urethanes, polyamides, polyimides, elastomers, nitinol, surgicalstainless steel, biopolymers (including extracellular matrix derivatives[cellular or acellular] with elastin, collagen, glycosaminoglycan andother constituents either in combination or separately), and/orcombinations thereof. Moreover, while the pressure apron 130 is shown inthe shape of a truncated cone it may also be formed in other shapes aswell including a cylinder, a disk and any other shape that has atissue-mating surface.

[0025] In use, the tissue-mating surface 160 of the pressure apron 130may be guided by a practitioner to a target tissue to be treated. Oncethe surface 160 reaches the target tissue it may be forcibly pushed intothe target tissue. Then, once the surface 160 is in position, theinjection tube 110 may be forced or urged into the target tissue. Afterentering the target tissue a therapeutic and plug forming material,compound or agent may be pushed down through the injection tube 110until it emerges from the channel at its distal end. As the compound isejected from the tube 110 the tube 110 may be drawn back towards thepressure apron 130 leaving a void that the compound can fill. Stillfurther, in a single use embodiment the pressure apron may becomedislodged after the injection has occurred and may remain at the targetsite and serve as a patch.

[0026] In a preferred embodiment the tube 110 will be withdrawn into thepressure apron 130 after the entire void has been filled with compound.During this time the pressure apron 130 will remain in place with thetissue-mating surface 160 sealably engaging the target site. It shouldpreferably remain there until such time as the compound has hardened toform an in-situ plug. Once formed, the pressure apron 130 may then bewithdrawn and the procedure repeated at a different point if necessary.To facilitate the adhesion of the tissue-mating surface 160 to thetarget tissue an adhesive may be used, a vacuum force may be applied,the pressure apron 130 may be shaped in the form of a suction cup tosealably engage the tissue-mating surface 160 to target tissue. Othermethodologies may be used as well.

[0027] The plug forming material and the therapeutic may be urged downthe injection tube 110 channel through various means including asyringe, a mechanical pump, and a squeezable bladder—each means locatedupstream of the distal end of the piercing tip 120. These means may beused not only to push the plug forming material and the therapeuticthrough the injection tube 110, but also to store the plug formingmaterial and the therapeutic prior to their use. Likewise, these meanscan be used to control the volume and rate of injection of the plugforming material and the therapeutic.

[0028] As noted above, the catheter 100 in this embodiment can be madefrom any suitably rigid material including rigid plastics. Similarly,the injection tube 110 can also be made from any suitably rigid materialcapable of carrying fluids. In either case, if the material can come incontact with a therapeutic or an in-situ plug forming compound it ispreferrable that the material be compatible with the therapeutic andcompound.

[0029] In the embodiment of FIGS. 1-3, the catheter 100 is fixed to thepressure apron 130. Alternatively, the catheter 100 may be slidablewithin the pressure apron 130 so that it can be slid back and forththrough the pressure apron 130 and extended from the pressure apron 130as necessary during a medical procedure. Similarly, the injection tube110 may be extended from the pressure apron 130 in various degrees orlengths depending on the required depth of injection.

[0030] In the present embodiment, as well as in other embodiments, thetherapeutic can be a in polymer solution. Moreover, in the dual lumen orchannel systems described below the polymer may include alginate, whilethe plug forming material can be, for example, a plug formingcross-linking agent such as calcium. Additional possible plug formingmaterials in dual lumen systems can include, but are not limited to, forexample, fibrin formed through an enzymatic-catalyzed reaction ofThrombin and Fibrinogen, and Sucrose Acetate Isobutyrate formed by theremoval of ethanol in an in-vivo aqueous environment therebyprecipitating a polymer.

[0031] The therapeutic traveling through the injection tube 110 in thisembodiment, as well as in the other embodiments, may also include, forexample, pharmaceutically active compounds, proteins, cells,oligonucleotides, ribozymes, anti-sense oligonucleotides, DNA compactingagents, gene/vector systems (i.e., any vehicle that allows for theuptake and expression of nucleic acids), nucleic acids (including, forexample, recombinant nucleic acids; platelets, dextran, glycosaminoglycans, carbohydrates; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNAin a non-infectious vector or in a viral vector and which further mayhave attached peptide targeting sequences; antisense nucleic acid (RNAor DNA); and DNA chimeras which include gene sequences and encoding forferry proteins such as membrane translocating sequences (“MTS”) andherpes simplex virus-1 (“VP22”)), and viral, liposomes and cationic andanionic polymers and neutral polymers that are selected from a number oftypes depending on the desired application. Non-limiting examples ofvirus vectors or vectors derived from viral sources include adenoviralvectors, herpes simplex vectors, papilloma vectors, adeno-associatedvectors, retroviral vectors, and the like. Non-limiting examples ofbiologically active solutes include antithrombogenic agents such asheparin, heparin derivatives, urokinase, and PPACK (dextrophenylalanineproline arginine chloromethylketone); antioxidants such as probucol andretinoic acid; angiogenic and anti-angiogenic agents and factors; agentsblocking smooth muscle cell proliferation such as rapamycin,angiopeptin, and monoclonal antibodies capable of blocking smooth musclecell proliferation; anti-inflammatory agents such as dexamethasone,prednisolone, corticosterone, budesonide, interleukin-10, serineprotease inhibitor, estrogen, sulfasalazine, acetyl salicylic acid, andmesalamine; calcium entry blockers such as verapamil, diltiazem andnifedipine; antineoplastic/antiproliferative/antimitotic agents such aspaclitaxel, 5-fluorouracil, methotrexate, doxorubicin, daunorubicin,cyclosporine, cisplatin, vinblastine, vincristine, epothilones,endostatin, angiostatin and thymidine kinase inhibitors; antimicrobialssuch as triclosan, cephalosporins, aminoglycosides, and nitorfurantoin;anesthetic agents such as lidocaine, bupivacaine, and ropivacaine;nitric oxide (NO) donors such as lisidomine, molsidomine, L-arginine,NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NOadducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, anRGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol,aspirin, prostaglandin inhibitors, platelet inhibitors and tickantiplatelet factors; vascular cell growth promotors such as growthfactors, growth factor receptor antagonists, transcriptional activators,and translational promoters; vascular cell growth inhibitors such asgrowth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; cholesterol-lowering agents; vasodilating agents; agentswhich interfere with endogeneus vascoactive mechanisms; survival geneswhich protect against cell death, such as anti-apoptotic Bcl-2 familyfactors and Akt kinase; and combinations thereof. Myoblasts, bone marrowderived stem cells, inesenchymal stem cells, and endothelial progenitorcells may also be used. Moreover, Cells can be of human origin(autologous or allogenic) or from an animal source (xenogeneic),genetically engineered if desired to deliver proteins of interest at theinjection site. The delivery mediated is formulated as needed tomaintain cell function and viability.

[0032] Polynucleotide sequences useful in practice of the inventioninclude DNA or RNA sequences having a therapeutic effect after beingtaken up by a cell. Examples of therapeutic polynucleotides includeanti-sense DNA and RNA; DNA coding for an anti-sense RNA; or DNA codingfor tRNA or rRNA to replace defective or deficient endogenous molecules.The polynucleotides of the invention can also code for therapeuticproteins or polypeptides. A polypeptide is understood to be anytranslation product of a polynucleotide regardless of size, and whetherglycosylated or not. Therapeutic proteins and polypeptides include as aprimary example, those proteins or polypeptides that can compensate fordefective or deficient species in an animal, or those that act throughtoxic effects to limit or remove harmful cells from the body. Inaddition, the polypeptides or proteins that can be injected, or whoseDNA can be incorporated, include without limitation, angiogenic factorsand other molecules competent to induce angiogenesis, including acidicand basic fibroblast growth factors, vascular endothelial growth factor,hif-1, epidermal growth factor, transforming growth factor α and β,platelet-derived endothelial growth factor, platelet-derived growthfactor, tumor necrosis factor α, hepatocyte growth factor and insulinlike growth factor; growth factors; cell cycle inhibitors including CDKinhibitors; anti-restenosis agents, including p15, p16, p18, p19, p21,p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase (“TK”) andcombinations thereof and other agents useful for interfering with cellproliferation, including agents for treating malignancies; andcombinations thereof. Still other useful factors, which can be providedas polypeptides or as DNA encoding these polypeptides, include monocytechemoattractant protein (“MCP-1”), and the family of bone morphogenicproteins (“BMP's”). The known proteins include BMP-2, BMP-3, BMP-4,BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11,BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16. Currently preferred BMP'sare any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimericproteins can be provided as homodimers, heterodimers, or combinationsthereof, alone or together with other molecules. Alternatively or, inaddition, molecules capable of inducing an upstream or downstream effectof a BMP can be provided. Such molecules include any of the “hedgehog”proteins, or the DNA's encoding them.

[0033] Organs and tissues that may be treated by the methods of thepresent invention include any mammalian tissue or organ, whetherinjected in vivo or ex vivo. Non-limiting examples include heart, lung,brain, liver, skeletal muscle, smooth muscle, kidney, bladder,intestines, stomach, pancreas, ovary, prostate, eye, tumors, cartilageand bone.

[0034] The therapeutics can be used, for example, in any application fortreating, preventing, or otherwise affecting the course of a disease ortissue or organ dysfunction. For example, the methods of the inventioncan be used to induce or inhibit angiogenesis, as desired, to prevent ortreat restenosis, to treat a cardiomyopathy or other dysfunction of theheart, for treating Parkinson's disease or a stroke or other dysfunctionof the brain, for treating cystic fibrosis or other dysfunction of thelung, for treating or inhibiting malignant cell proliferation, fortreating any malignancy, and for inducing nerve, blood vessel or tissueregeneration in a particular tissue or organ.

[0035]FIGS. 4A through 4D each show cross-sectional views of a tissuetarget 400 and a dual channel injection catheter 470 as being employedin accordance with another embodiment of the present invention. Thesefigures show sequential steps beginning with the placement of thecatheter 470 against the target tissue, the formation of the in-situplug 494, and the release of therapeutic to the surrounding area.

[0036] In FIG. 4A, the dual channel injection catheter 470 is shownfollowing its placement against the target tissue 400 such that thepressure apron 430 is preferably sealably engaging the target tissue400. FIG. 4A further shows the first and second channels 411, 412positioned within the catheter prior to their insertion into the targettissue 400. Also visible in FIG. 4A is the preferred orientation of thepressure apron 430 wherein the larger side of the pressure apron 430 isoutwardly facing.

[0037]FIG. 4B shows the dual channel injection catheter 470 with thefirst channel and second channels 411 and 412 being urged through thepressure apron into the target tissue 400. As can be seen, the piercingtip 480 of the second channel 412 has penetrated into the target tissue400 to form a void 470 in the target tissue 400. As can also be seen thefirst channel 411 and the second channel 412 have moved in tandem.Alternatively, in other embodiments, these channels may moveindependently as needed.

[0038] Next, in FIG. 4C, the first and second channel, have beenpartially retracted out of the target tissue 400 in the direction ofarrow 490. During this step, as can be seen, the pressure apron 430 hasremained sealably engaged with the target tissue 400. Also, as indicatedby arrows 492 and 493, in-situ plug forming material and therapeutic arebeing injected into the void 475 during this step.

[0039] Dependent upon the properties of the plug forming material andthe therapeutic, they may each be concurrently ejected as the injectiontube 410 is withdrawn. They may also be delivered only after theinjection tube 410 has reached its fully retracted position. Their fullyretracted position is shown in FIG. 4D, which also shows the plug in afully formed state releasing therapeutic to the target tissue asindicated by arrows 491. Once the plug 494 has been formed the pressureapron 430 may be removed. The plug forming or cross-linking agentinjected into the void can be any one of numerous plug forming materialsincluding calcium and thrombin.

[0040]FIG. 5 is an enlarged side view of a dual-channel injectioncatheter system 500 according to another alternative embodiment of thepresent invention. In this embodiment, an outer catheter 503 has a lumen513 and contains an injection tube 520 having first and second channels514 and 515. Both the injection tube 520 and the catheter end inpiercing tips 524 and 523. The catheter is surrounded by pressure apron530 in this embodiment.

[0041] The outer catheter 503 may be slidably positioned within thepressure apron 530 in this embodiment. Therefore, it may be used to formthe void for the therapeutic with its piercing tip 523 and may then beretracted back before the piercing tip 524 of the first and secondchannels is advanced further into the target tissue. In order to providefor a sealable engagement with the target tissue, if the outer catheter503 is slidable within the pressure apron, it should be lockable withinthe apron in its retracted position so that an adequate amount of forcemay be placed on the pressure apron by the catheter system 500 tomaintain a seal with the target tissue.

[0042] The first and second channels 514 and 515 may be independentlymoveable and can be extended from and retracted into the pressure apron530 individually or in tandem as required by the procedure beingperformed. For instance, in one embodiment, after the pressure apron 530has been placed up against a target tissue, both the first channel 514and the second channel 515 may be concurrently advanced into the targetarea. Then, a plug forming matrix, compound or material may be injectedfrom the first channel 514 while the second channel 515 remains fullyextended into the tissue. After the plug forming matrix has been allowedto set up therapeutic may then be ejected from the second channel 515into the plug forming matrix as the second lumen is retracted from thetarget area. By fabricating the plug in this fashion, the therapeuticcan be interfaced with the plug forming matrix after it has begun to setup rather than in conjunction with it. Once the in-situ plug has formedthe pressure apron 530 may then be removed from the target area and theprocedure may be repeated.

[0043] In the present embodiment, as with the others and as suggestedabove, the therapeutic can be a polymer solution including, for example,alginate, while the plug forming material can be, for example, a plugforming, cross-linking agent such as calcium. Additional possible plugforming materials can include, but are not limited to, for example,fibrin, formed through an enzymatic-catalyzed reaction of Thrombin andFibrinogen, and Sucrose Acetate Isobutyrate formed by the removal ofethanol in an in-vivo aqueous environment thereby precipitating apolymer.

[0044]FIG. 6 is a cross-sectional view of the dual channel injectioncatheter of FIG. 5 taken along line 6-6 showing one possible arrangementof the first channel 514 and the second channel 515. In FIG. 6, thesecond channel 515 is shown to be larger than the first channel 514.However, in an alternate embodiment the first and second channels can bethe same size. Additionally, while the first and second channels areshown longitudinally side by side, in alternate embodiments, anyarrangement can be used, including, for example, having one channelsurrounding the other. Furthermore, the present invention is notintended to be limited to one or two channel injection tubes as three ormore may also be employed. Likewise, the channels and lumens need not beconcentric but may also be positioned side by side an in otherorientations as well.

[0045]FIG. 7 shows a cross-sectional view of a human heart 700 with oneembodiment of the present invention located therein. In FIG. 7 theinjection catheter 730 having a piercing tip 720 and a pressure apron725 threaded through an aortic artery 715 into the left ventricle 710 ofthe heart 700 can be seen. While the injection catheter is shownthreaded though the aortic artery, it may also be threaded through thefemoral, brachial, and carotid artery.

[0046] In-situ plugs 740, formed in accordance with the presentinvention can be clearly seen in FIG. 7.

[0047]FIG. 8 shows a side view of another alternative embodiment of thepresent invention. Visible in FIG. 8 is the catheter 800, the firstchannel feed 810, the second channel feed 820, catheter wall 803,pressure apron 830, first channel 805, second channel 815, piercing tip823, injection tube 825, and piercing tip 824. In this embodiment thepressure apron is shown as a metal cylinder and the channel feeds, whichallow for the insertion of therapeutic and plug forming material, arepositioned at the proximal end of the catheter.

[0048] The use of in-situ plugs to deliver large molecules in accordwith the present invention have been proven to be plausible method ofdelivery. FIG. 9 is a graph of a scaling group, proving this, showingtheoretical delivered mass versus observed delivered mass. In FIG. 9,results are presented for a three solution scaling group used in adirect injection FITC-Dextran delivery scaling test. The three solutionshad theoretical delivered masses of 25.4, 49.4 and 99.6 micrograms (ug)as shown along the x-axis of FIG. 9. The observed delivered masses forthe three solutions are 24.2, 36.8 and 92 ug, respectively, as shownalong the y-axis.

[0049]FIG. 10 is a graph of a control group, also addressing the issueof therapeutic delivery, showing a control system versus observeddelivered mass. In FIG. 10, results are presented for a three solutioncontrol group used in a direct injection FITC-Dextran delivery controlstest. The controls used included Alginate, Ca2+ and Dextran. Each of thethree solutions had theoretical delivered masses of 50 ug as shown alongthe x-axis of FIG. 10. The observed delivered masses for the threesolutions are 44.7, 58.8 and 47.9 ug, respectively, as shown along they-axis.

[0050] The test procedure followed to obtain the scaling group andcontrol group results shown in FIG. 9 and FIG. 10 was designed to verifywhether the concentration of released agent is equal to the expected.Specifically, the procedure involved the following steps: Prepare 40 gof a 2.5% (w/w) Alginate solution (aqueous).

[0051] 1. Prepare a 0.6M CaCl₂ solution (aqueous).

[0052] 2. Prepare an agarose gel:

[0053] 3. In a 50 ml beaker mix 2.5% (w/w) agarose with water.

[0054] 4. Heat agarose mixture in a microwave until steadily boiling.(Solution should be completely clear.)

[0055] 5. Using heat-protective glove(s), remove the beaker from themicrowave and pour the hot gel into a tin weighing pan until the liquidlevel is almost to the top of the weighing pan.

[0056] 6. Cover the gel and allow it to cool for 30 minutes. (The gelshould be used on the same day it is made.)

[0057] 7. Prepare FITC-Dextran injection solutions according to thefollowing chart: Mass Volume Volume Solution [Dextran] Dextran AlginateCaCl₂ Volume Number (mg/ml) (mg) (mL) (mL) Water (mL) 1 2.5 12.5 5 — — 25 25 5 — — 3 10 50 5 — — 4 5 25 — 5 — 5 5 25 — — 5 6 5 25 5 — —

[0058] 1. In a darkened room load approximately 100 ul of the CaCl₂solution and 100 uL of the Alginate solution into their respectivesyringes.

[0059] 2. Prepare for injection by dispensing both materials until eachis just about to emerge from the tip of the catheter (approximately thevoid volume shown above).

[0060] 3. Insert the needle tip into the agarose gel until pressureapron is firmly set against surface of gel.

[0061] 4. Dispense 10 uL of the Alginate and 2 uL of the CaCl₂ andquickly remove needle from gel.

[0062] 5. Visually inspect for plug placement.

[0063] 6. Remove syringes and flush each needle with water and air.

[0064] 7. Reload and repeat these steps (n=3 for each solution).

[0065] The analysis of the results from the above tests involved:

[0066] Razor blade to cut a cube out of the gel approximately 0.5 cmaround the injection site.

[0067] 1. Cut 2 mandrills such that they can fit into a 20 mLscintillation vial.

[0068] 2. Use to mandrills in tandem to break up the agarose cube withina 20 mL vial.

[0069] 3. Leave the mandrills in the vial and fill with 10 mL PBS.

[0070] 4. Cap the vial and allow the contents to incubate underagitation and light cover for 17 to 24 hours.

[0071] 5. Aliquot 200 mL from each vial for flourometry.

[0072] 6. Flourometry is set for 490 nm excitation and 520 nm emission.7. Multiplying the resulting [Dextran] by 10 mL to get the total mass ofextracted Dextran.

[0073] An injection catheter device and a method for delivering atherapeutic that can form into a plug in-situ are provided. Variousembodiments of the injection catheter and methods of use thereof aredescribed above including a catheter having a first lumen in fluidcommunication with a pressure source and a piercing tip, and a pressureapron having a tissue-mating surface for sealably engaging a targettissue and the catheter slidably placed through the pressure apron. Itshould be appreciated that the above provided embodiments are merelyillustrative and other embodiments, modifications, and variations of thepresent invention are also plausible and may be made without departingfrom the spirit and scope of the present invention.

What is claimed is:
 1. An injection catheter for direct injection into abody tissue comprising: an injection tube having a first channel and apiercing tip, the first channel in fluid communication with a pressuresource; and a pressure apron, the injection tube slidably placed in thepressure apron and moveable from a first position to a second position,the pressure apron having a tissue-mating surface, the piercing tipextending beyond the tissue-mating surface in the second position. 2.The injection catheter of claim 1, wherein the injection tube has asecond channel.
 3. The injection catheter of claim 1, furthercomprising: a catheter wall surrounding the injection tube and coupledto the pressure apron.
 4. The injection catheter of claim 1, wherein thepressure apron includes an adhesive on at least a portion of one of itssurfaces.
 5. The injection catheter of claim 1, wherein the pressureapron is in the form of a truncated cone.
 6. The injection catheter ofclaim 1, wherein the pressure apron includes a biocompatible polymericmaterial selected from silicones, nylons, urethanes, polyamides,polyimides, elastomers, or combinations thereof.
 7. The injectioncatheter of claim 1, further comprising: a second injection tubeslidably placed in the pressure apron.
 8. An injection device for directinjection into a body tissue comprising: a catheter with a lumen; apressure apron coupled to the catheter and surrounding the lumen; and, apiercing tip retractably positioned within the lumen and extendable fromthe pressure apron, the pressure apron having a tissue-mating surfaceadaptable to sealably engage a target tissue.
 9. The injection device ofclaim 8, wherein the piercing tip has a first channel and a secondchannel, the first and second channels in fluid communication with apressure source.
 10. The injection device of claim 8, wherein a channelcoupled to the piercing tip contains therapeutic.
 11. The injectiondevice of claim 8, wherein a channel coupled to the piercing tipcontains plug forming material.
 12. The injection device of claim 8,wherein the pressure apron has an adhesive on one of its surface. 13.The injection device of claim 12, wherein the adhesive is selected frompolysacharides, cellulose, hydrogels, aliginate, or combinationsthereof.
 14. The injection device of claim 8 wherein the target tissueis the myocardium.
 15. A medical kit for delivering a therapeuticcomprising: a catheter having a channel, and a piercing tip, thepiercing tip in fluid communication with a pressure source the piercingtip slidably placed in the channel; a pressure apron coupled to thecatheter and having a tissue-mating source; and a therapeutic.
 16. Thekit of claim 15, wherein the piercing tip has a first lumen and a secondlumen, the first lumen and the second lumen slidable relative to oneanother.
 17. The kit of claim 15, wherein the pressure apron sealablyengages the catheter.
 18. The kit of claim 15, wherein the pressureapron includes an adhesive on a least a portion of one of its surfaces.19. The kit of claim 15, wherein the pressure apron is in the form of atruncated cone.
 20. The kit of claim 15, wherein the pressure apronincludes a biocompatible polymeric material selected from silicones,nylons, urethanes, polyamides, polyimides, elastomers,polyetherblockamide or combinations thereof.
 21. A system for preventingleakage of material from a body tissue during the injection of atherapeutic comprising: a catheter with a lumen; a pressure apronsurrounding the lumen; and, a piercing tip retractably positioned withinthe lumen, the pressure apron having a tissue-mating surface.
 22. Thesystem of claim 21 wherein the piercing tip has a first channel and asecond channel, the first and second channels in fluid communicationwith a pressure source.
 23. The system of claim 21 wherein the firstchannel of the piercing tip contains a therapeutic and the secondchannel of the piercing tip contains a plug forming material.
 24. Thesystem of claim 21 wherein the pressure apron has an adhesive on atleast a portion of one of its surfaces.
 25. The system of claim 24wherein the adhesive is selected from polysacharides, cellulose,hydrogels, aliginate, or combinations thereof.